Magnetic Resonance Imaging (hereinafter “MRI”) is a powerful imaging tool that produces results analogous to x-ray images without requiring the application of harmful radiation. The nuclei of many atoms have a property called spin, which is associated with a small magnetic moment. In the absence of an external magnetic field, the distribution of the orientations of these magnetic moments is random. In the presence of a static external magnetic field, the nuclear magnetic moments precess about the field direction, producing a net alignment in the field. MRI works by exciting the molecules of a target object using a harmless pulse of radiofrequency (“RF”) energy to excite molecules that have first been aligned using a strong external magnetic field and then measuring the molecules rate of return to an equilibrium state within the magnetic field following termination of the RF pulse.
For example, in NMR imaging, a patient is placed in a static field and a short radio frequency pulse is applied via a coil surrounding the patient. The radio frequency or RF signal is selected for the specific nuclei (e.g. 1H) that are to be resonated. The RF pulse causes the magnetic moments of these nuclei to align with the new field and to precess in phase. On termination of the pulse, the moments return to the original distribution of alignments with respect to the static field and to a random distribution of precession phases, thereby giving off a nuclear magnetic resonance signal that can be picked up by a receiving coil. The NMR signal represents a proton density map of the tissue being studied.
Two additional values can be determined when the RF pulse is turned off and the nuclear magnetic moments are relaxing or returning to equilibrium orientations and phases. These are T1 and T2, the spin-lattice and spin-spin relaxation times. T1 represents a time characteristic of the return to equilibrium spin distribution, equilibrium alignment of the nuclear magnetic moments in the static field. T2, on the other hand, represents a time characteristic of the return to random precession phase distribution of the nuclear magnetic moments. Hence, the NMR signal that is generated may contain information on proton density, T1 and T2. The visually readable images that are generated as output are the result of computer data reconstruction on the basis of that information.
Because successful imaging depends on the ability of the computer to recognize and differentiate between different types of tissue, it is not uncommon to apply a contrast agent to the tissue prior to making the image. The contrast agent alters the response of the aligned protons to the RF signal. Good contrast agents interact differently with different types of tissue, with the result that the effect of the contrast agent is greater on certain body parts, thus making them easier to differentiate and image. Various contrast agents are known for various medical imaging techniques, including X-ray, magnetic resonance and ultrasound imaging. Magnetic resonance contrast agents generally function by modifying the density or the characteristic relaxation times T1, and T2 of the water protons, which results in resonance signals from which the images are generated.
Thus, a need exists for contrast agents having improved properties (e.g., in terms of contrast enhancement, water-solubility, biodistribution, stability, opacity, relaxivity, or tolerability).